[Show abstract][Hide abstract] ABSTRACT: Recently, log odds of positive lymph nodes (LODDS) was proven a better prediction of outcomes than other methods in gastric cancer, pancreatic cancer, and colon cancer. However, the validity is not yet tested in oral cavity squamous cell carcinoma (OSCC). We conducted a retrospective study to compare the predictive ability of LODDS, traditional pN classification and lymph node ratio (rN) in OSCC patients.
In total, 347 OSCC patients receiving surgery with or without adjuvant therapy at the time of diagnosis between 2004 and 2013 were identified from the cancer registry database of the Dalin Tzu Chi Hospital. Cox proportional hazards models were used to compare the disease-specific survival (DSS) rates for pN, rN, and LODDS after adjusting for possible confounding risk factors. The discriminatory ability of different classification systems was evaluated using the adjusted hazard ratio and Akaike information criterion (AIC) by multivariate regression model. The prediction accuracy of the model was assessed by Harrell's c-statistic.
The 347 OSCC patients had a mean age of 57 years old. Among them, 322 patients (92.8%) were male and 189 patients (54.5%) were in stages III to IV. LODDS showed better discriminatory ability for patients with <5 pathological cervical metastatic nodes and those with rN < 0.2. The hypothetical T-LODDS-M staging system had higher linear trend Chi-square, lower AIC, and higher prediction accuracy compared with the American Joint Committee on Cancer (AJCC) TNM, or hypothetical T-rN-M system. After adjusting for other factors, the LODDS unfavorable group had the highest adjusted hazard ratio (HR, 5.42; 95% confidence interval [CI], 3.19–9.12) and LODDS-based model lowest AIC of 704, comparing with pN and rN-based model. The LODDS-based system had the highest prediction accuracy for 3-year DSS (Harrell's c-statistic, 0.803).
In our series, LODDS shows great promise as a prognostic tool for OSCC. Compared with the AJCC pN classification and the rN classification, LODDS can stratify OSCC patients and help to identify high-risk patients missed by the other systems.
[Show abstract][Hide abstract] ABSTRACT: To evaluate effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) inoculated during defined “vaccination period,” first 6 months post cancer diagnosis (ie, an anti-cancer treatment period), in elderly lung cancer patients on community-acquired pneumonia (CAP) hospitalization incidence.
This was a nationwide population-based cohort study of 157 newly diagnosed elderly lung cancer patients receiving PPSV23 during “vaccination period”, and 628 age and sex one-to-one matched controls enrolled in the National Health Insurance Research Database (NHIRD) of Taiwan between 2007 and 2010. All patients were ≥75 years old and still survival post “vaccination period.” Incidence density (ID) of all-cause inpatient CAP and cumulative survival risk were analyzed by multivariate Poisson regression and Kaplan–Meier method, respectively.
After a 4-year follow-up, IDs of all-cause inpatient CAP for vaccination and control cohorts were 297 and 444 per 1000 PYs, respectively. Less vaccinated patients had CAP incidence density >1 time per PY (12.7% vs 21.2%) than non-vaccinated patients. After adjusting for potential confounding variables, like influenza vaccination, comorbidities, cancer treatment modalities, and socioeconomic status, adjusted inpatient CAP incidence rate in PPSV23 vaccination cohort was 0.74 times lower than control cohort (incidence rate ratio [IRR] = 0.740, P = 0.0339). Two-year cumulative CAP hospitalization rates and overall survival rates were 37.1% vs. 55.4%, and 46.6% vs. 26.2%, respectively, for lung cancer patients with and without PPSV23 (both P < 0.001). Subgroup analysis showed that for elderly lung cancer patients not ever receiving influenza vaccine, PPSV23 still had trend to reduce all-cause inpatient CAP.
For elderly lung cancer patients aged ≥75 years, PPSV23 inoculated during anti-cancer treatment period could reduce CAP hospitalizations and improve survival.
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with a high mortality rate. The optimal therapeutic choice for early HCC is surgical resection. However, the rate of intrahepatic recurrence is high. The objective of this study was to evaluate the effect of various factors on the survival of patients with early HCC. Between January 1st, 2006 and December 31st, 2013, a total of 89 patients who underwent surgery for HCC were retrospectively enrolled. The analysis was conducted using the Student's t-test, Chi-square test, Kaplan-Meier method and Cox proportional hazard regression model to assess potential confounding and predictive variables. The 3-year overall survival (OS) rate was 71%. The 3-year OS rates in patients with and those without vascular invasion were 62.1 and 92.8%, respectively (P<0.003). Based on the multivariate analysis, postoperative pathological vascular invasion (hazard ratio = 4.96; 95% confidence interval: 1.55-15.9) remained an independent predictor of adverse long-term outcome. Furthermore, vascular invasion was significantly associated with intrahepatic metastasis. These data emphasize the need for effective adjuvant therapy in selected high-risk patients with early HCC. Further studies are required to determine the optimal approach to further improving the prognosis of early HCC.
Preview · Article · Jan 2015 · Molecular and Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: The association of chronic hepatitis B virus (HBV) infection with end-stage renal disease (ESRD) is unclear. To help clarify this we conducted a nationwide cohort study to measure the association by analyzing the claims data from the Taiwan National Health Insurance Research Database with ICD-9 codes used to identify diseases. We identified 17,758 adults who had chronic HBV infection and had not taken nucleos(t)ide analogs from 1999 to 2010 and randomly selected 71,032 matched controls without HBV in the same data set. The risk of ESRD was compared between these two cohorts. Cumulative incidences and hazard ratios were calculated after adjusting for competing mortality. The risk of ESRD was significantly higher in the HBV cohort (12-year cumulative incidence, 1.9%) than in the non-HBV cohort (0.49%) with a significant adjusted hazard ratio of 3.85. Multivariable stratified analysis further verified significant associations of ESRD with HBV in men of any age and women under the age of 60 years, but no significant association in women aged ⩾60 years. Thus, a large national cohort study indicates that untreated chronic HBV infection is associated with increased risk of ESRD. Hence, high-risk HBV-infected patients should have targeted monitoring for the development of ESRD.Kidney International advance online publication, 26 November 2014; doi:10.1038/ki.2014.363.
Full-text · Article · Nov 2014 · Kidney International
[Show abstract][Hide abstract] ABSTRACT: Radioresistance is still an emerging problem for radiotherapy of oral cancer. Aberrant epigenetic alterations play an important role in cancer development, yet the role of such alterations in radioresistance of oral cancer is not fully explored. Using a methylation microarray, we identified promoter hypermethylation of FHIT (fragile histidine triad) in radioresistant OML1-R cells, established from hypo-fractionated irradiation of parental OML1 radiosensitive oral cancer cells. Further analysis confirmed that transcriptional repression of FHIT was due to promoter hypermethylation, H3K27me3 and overexpression of methyltransferase EZH2 in OML1-R cells. Epigenetic interventions or depletion of EZH2 restored FHIT expression. Ectopic expression of FHIT inhibited tumor growth in both in vitro and in vivo models, while also resensitizing radioresistant cancer cells to irradiation, by restoring Chk2 phosphorylation and G2/M arrest. Clinically, promoter hypermethylation of FHIT inversely correlated with its expression and independently predicted both locoregional control and overall survival in 40 match-paired oral cancer patient samples. Further in vivo therapeutic experiments confirmed that inhibition of DNA methylation significantly resensitized radioresistant oral cancer cell xenograft tumors. These results show that epigenetic silencing of FHIT contributes partially to radioresistance and predicts clinical outcomes in irradiated oral cancer. The radiosensitizing effect of epigenetic interventions warrants further clinical investigation.
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this study is to evaluate the liver metastasis risk among colorectal cancer patients with liver cirrhosis.
This was a nationwide population-based cohort study of 2973 newly diagnosed colorectal cancer patients with liver cirrhosis and 11 892 age-sex matched controls enrolled in Taiwan between 2000 and 2010. The cumulative risk by Kaplan-Meier method, hazard ratio by the multivariate Cox proportional model and the incidence density were evaluated.
The median time interval from the colorectal cancer diagnosis to the liver metastasis event was 7.42 months for liver cirrhosis group and 7.67 months for non-liver cirrhosis group. The incidence density of liver metastasis was higher in the liver cirrhosis group (61.92/1000 person-years) than in the non-liver cirrhosis group (47.48/1000 person-years), with a significantly adjusted hazard ratio of 1.15 (95% CI = 1.04-1.28, P = 0.007). The 10-year cumulative risk of liver metastasis for the liver cirrhosis and the non-liver cirrhosis group was 27.1 and 23.6%, respectively (P = 0.006). For early cancer stage with locoregional disease patients receiving surgery alone without adjuvant anti-cancer treatments, patients with liver cirrhosis (10-year cumulative risk 23.9 vs. 15.7%, P < 0.001) or cirrhotic symptoms (10-year cumulative risk 25.6 vs. 16.6%, P = 0.009) both still had higher liver metastasis risk compared with their counterparts. For etiologies of liver cirrhosis, the 10-year cumulative risk for hepatitis B virus and hepatitis C virus, hepatitis B virus, hepatitis C virus, other causes and non-liver cirrhosis were 29.5, 28.9, 27.5, 26.7 and 23.4%, respectively, (P = 0.03).
Our study found that liver metastasis risk was underestimated and even higher in colorectal cancer patients with liver cirrhosis.
Full-text · Article · Nov 2014 · Japanese Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Objectives
Increased caseload has been associated with better patient outcomes in many areas of health care, including high-risk surgery and cancer treatment. However, such a positive volume vs. outcome relationship has not yet been validated for cervical cancer brachytherapy. The purpose of this study was to examine the relationship between physician caseload and survival rates in cervical cancer treated with brachytherapy using population-based data.Methods
Between 2005 and 2010, a total of 818 patients were identified using the Taiwan National Health Insurance Research Database. Multivariate analysis using a Cox proportional hazards model and propensity scores was used to assess the relationship between 5-year survival rates and physician caseloads.ResultsAs the caseload of individual physicians increased, unadjusted 5-year survival rates increased (P¿=¿0.005). Using a Cox proportional hazard model, patients treated by high-volume physicians had better survival rates (P =0.03), after adjusting for comorbidities, hospital type, and treatment modality. When analyzed by propensity score, the adjusted 5-year survival rate differed significantly between patients treated by high/medium-volume physicians vs. patients treated by low/medium-volume physicians (60% vs. 54%, respectively; P¿=¿0.04).Conclusions
Provider caseload affected survival rates in cervical cancer patients treated with brachytherapy. Both Cox proportional hazard model analysis and propensity scores showed association between high/medium volume physicians and improved survival.
Full-text · Article · Oct 2014 · Radiation Oncology
[Show abstract][Hide abstract] ABSTRACT: Modern radiation therapy strives to minimize injury to organs while increasing the anticancer effects. The present study aimed to investigate the radiosensitizing effects of everolimus and to examine the molecular mechanisms responsible for everolimus‑mediated radiosensitization. Radiation in combination with everolimus (30 nM) sensitized Ras-transformed cells to radiation in vitro. Radiation induced apoptotic markers (sub-G1 cell accumulation, membrane inversion and DNA fragmentation) and treatment with everolimus did not promote radiation-induced apoptosis. However, LC3-II expression increased following combination treatment with everolimus and radiation, and the radiosensitizing effects of everolimus were reversed following transfection with small interfering RNA (siRNA) targeting Beclin 1. In addition, the protein levels of activated S6 kinase 1 (S6K1) were significantly reduced following treatment with everolimus, and the phosphorylation of factor 4E binding protein 1 (4EBP1) was suppressed following combination treatment. Taken together, our data demonstrate that everolimus sensitizes Ras-transformed cells to radiation in vitro. Everolimus-mediated radiosensitization is associated with the autophagy pathway. Thus, everolimus is a novel radiosensitizing agent with potential for use in cancer radiotherapy.
Preview · Article · Sep 2014 · International Journal of Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: Background
The utility of lymph node ratio (LNR) in predicting outcomes has been reported previously. In current study, we further subgroup by LNR in subjects with lymph nodes metastasis of colorectal cancer, breast cancer, and head and neck cancer.
Cancers with pathological lymph node metastasis (pN+) at time of diagnosis between 2004 and 2012 were identified from the cancer registry database of the Dalin Tzu Chi General Hospital. The Kaplan–Meier method with log-rank test and the Cox proportional hazards model were used to compare the disease-specific survival (DSS) rates for different LNR after adjusting for possible confounding risk factors.
A total of 431 cancer patients with pN+ were eligible in the current study: 149 patients with colorectal cancer; 141 patients with breast cancer; and 141 patients with head and neck cancer. High LNR was associated with poor DSS rates with the mean 24–45 months of follow-up period. In the multivariate analysis, high LNR was an independent poor prognostic factor in colorectal cancer (LNR ≥ 0.5; HR 4.10; p
No preview · Article · Aug 2014 · Journal of Cancer Research and Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Objective
Hepatocellular carcinoma (HCC) is a common cause of cancer mortality. Resection is the best choice for HCC. Our objective was to evaluate the impact of various factors that affected survival in patients with resectable HCC.
Materials and methods
Between January 1, 2007 and December 31, 2013, 107 patients with a diagnosis of HCC who underwent surgery were enrolled retrospectively. The analysis was carried using t tests, the Kaplan–Meier method, and Cox proportional hazard regression model to identify potential confounding and predicting variables.
The 3-year overall survival rates in patients with surgical margins >1 mm and ≤1 mm were 79% and 59% (p = 0.02), respectively, and those in patients with and without vascular invasion were 57% and 93% (p < 0.001), respectively. Based on multivariate analysis, postoperative pathological vascular invasion (hazard ratio, 6.25; 95% confidence interval, 2.01–19.37) and surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.14–0.96) remained independent predictors of an adverse long-term outcome.
Patients with vascular invasion combined with surgical margins ≤1 mm are at risk of poor survival and have a worse locoregional control rate. Further studies are warranted to identify the optimal strategy for the prevention and management of intrahepatic recurrence in order to further improve the prognosis of HCC after resection.
No preview · Article · Jun 2014 · Tzu Chi Medical Journal
[Show abstract][Hide abstract] ABSTRACT: A high risk of stroke occurrence has been reported in several types of irradiated cancer patients. However, clinical data are lacking in irradiated lung cancer patients. The present study intended to explore a risk level of ischemic stroke occurrence in irradiated lung cancer patients.
A nationwide population-based database obtained from the Taiwan National Health Insurance was analyzed. Between 2003 and 2006, we recruited 560 resected lung cancer patients into two study groups: surgery-plus-irradiation (n = 112) and surgery-alone (n = 448). Patients treated with chemotherapy were excluded. Propensity score match was used for pairing cases with a ratio of 1∶4. Two-year ischemic-stroke-free survival was defined as the primary endpoint.
Three observations supported a high risk of ischemic stroke occurrence in patients with postoperative irradiation when compared with those patients with surgery alone: first, a high incidence per 1,000 person-year (22.3 versus 11.2, 1.99 folds); second, a low two-year ischemic-stroke-free survival rate (92.2% versus 98.1%, P = 0.019); and third, a high adjusted hazard ratio (HR, 4.19; 95% CI, 1.44-12.22; P = 0.009). More notably, the highest risk of ischemic stroke occurrence was found in irradiated patients who had diabetes mellitus (HR, 34.74; 95% CI, 6.35->100; P<0.0001).
A high incidence of ischemic stroke was observed in irradiated lung cancer patients, especially in those with diabetes mellitus. For these patients, close clinical surveillance and strict diabetes control should be considered. Further studies to define detail biological mechanisms are encouraged.
[Show abstract][Hide abstract] ABSTRACT: Background: Traditional Chinese medicine (CM) appears to be used worldwide, especially by cancer patients. The aim of the present study was to explore CM uses and CM non-users by patients with colorectal cancer (CRC).
Materials and methods: A retrospective study was conducted using registration and claims data sets for 2007 from the National Health Insurance Research Database. Patients with colorectal cancer were identified from the Registry for Catastrophic illness Patients. Binary logistic regression was used to estimate odds ratios as the measure of association with the use of CM.
Results: A total of 61,211 CRC patients diagnosed in 2007 were analysis. Most CM users preferred to visit private clinics (46.9%) with 306,599 visits. In contrast, the majority of CM non-users preferred to visit private hospitals (42.2%) with 538,769 visits. Among all 176,707 cancer-specific CM visit, there were 66.6% visits to CM outpatient department (OPD) of private hospitals, while in 477,612 non-cancer-specific CM visits, 62.0% was for private clinics. The proportion of expenses for diagnostic fees for CM user in CM visits was much less than that for WM visits and CM non-users (US$4.6 vs. 29.3 vs. 33.5). The average cost for CM user in CM was less than that for WM visits and CM non-users (US$6.3 vs. 25.9 vs. 30.3). Female patients, younger age, and patients not living in the northern region, with higher EC or more comorbidities were more likely to receive CM treatment.
Conclusion: The prevalence and costs of insurance-covered CM among CRC patients were low. Further longer longitudinal study is needed to follow up this trend.
Full-text · Article · Feb 2014 · African Journal of Traditional, Complementary and Alternative Medicines
[Show abstract][Hide abstract] ABSTRACT: Radiotherapy (RT) or concurrent chemoradiation therapy has been suggested to increase the risk of coronary heart disease for cervical cancer patients, but the results of studies have been inconsistent. Therefore, we aimed to investigate the factors which influence the risk of developing myocardial infarction (MI) in cervical cancer patients with a large, nationwide cohort.
The study analyzed data from the 1996 to 2010 National Health Insurance Research Database provided by the National Health Research Institutes in Taiwan. The assessed number of patients with cervical cancer with radiotherapy only, surgery with bilateral oophorectomy only, and with appendectomy were 308, 323 and 229, respectively. The Kaplan-Meier method and the Cox proportional hazards model were used to assess the risk of myocardial infarction.
The adjusted hazard ratio for cervical cancer in patients with MI was 1.97 (95% CI, 0.97 - 3.91; P = 0.05) for the group that received RT alone, and 2.13 (95% CI, 1.11 - 3.75; P = 0.01) for the surgery group when compared with controls. The more risk comorbidities they have, the higher the risk of myocardial infarction would be for the patients.
The incidence of MI was significantly higher among cervical cancer patients with RT alone or surgery with bilateral oophorectomy alone than among general populations. RT might be as a factor to increase risk as bilateral oophorectomy. Whether RT itself triggers menopause or impairs the ovarian hormone production that increases the risk of MI needs to be further investigated.
Full-text · Article · Dec 2013 · Journal of Clinical Medicine Research
[Show abstract][Hide abstract] ABSTRACT: The association of hepatitis C virus (HCV) infection with chronic kidney disease (CKD) remains widely debated. Here we quantify this association by analysis of data from the Taiwan National Health Insurance Research Database and ICD-9 codes to identify 9430 adults with newly diagnosed HCV (years 1999-2006) and randomly selected 37,720 matched non-HCV control individuals. The incidence rate and risk of incident CKD were evaluated through the end of 2010. The frequency of CKD was 1.66-fold higher in the HCV than the non-HCV cohort (5.46 compared with 3.43 per 1000 person-years), and the adjusted hazard ratio remained significant at 1.28 (95% confidence interval, 1.12-1.46). A multivariate analysis was used to determine the influence of HCV on CKD risk with regard to age, gender, follow-up duration, and comorbidities. The risk for CKD in HCV-infected individuals was higher with diabetes, hyperlipidemia, and cirrhosis (8.44; 3.70-19.23), followed by men <50 years (2.32; 1.49-3.61), all individuals <50 years (1.90; 1.33-2.73), men overall (1.44; 1.22-1.71), and individuals followed for 6 years (1.35; 1.06-1.71); all with considerable significance. Thus, HCV infection is associated with an increased risk of CKD. Hence, high-risk HCV-infected individuals should be aggressively monitored for development of CKD.Kidney International advance online publication, 20 November 2013; doi:10.1038/ki.2013.455.
Full-text · Article · Nov 2013 · Kidney International
[Show abstract][Hide abstract] ABSTRACT: Three-dimensional conformal radiation therapy (3DCRT) has emerged as a preferred treatment for gynecologic malignancies. Yet its superiority to conventional radiotherapy (2-dimensional radiotherapy (2DRT)) for gynecologic malignancies has not been well established. Data from the 2005 to 2010 National Health Insurance Research Database (NHIRD) provided by the National Research Institutes in Taiwan were analyzed to address this issue. Patients were initially diagnosed as having cervical cancer according to the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) code 180, and this clinical diagnosis was confirmed histopathologically or cytologically. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the reported data. Between January 2005 and December 2010, there were 776 patients with newly diagnosed cervical cancer without metastasis, local recurrence, or surgical treatment before RT and 132 and 644 patients, respectively, who received 2DRT and 3DCRT. After adjustment for age, diabetes mellitus, hypertension, coronary heart disease, hyperlipidemia, side effects, urbanization level, geographic region, and enrollee category in the 5-year follow-up period, the HR was 1.82 (95% CI, 1.16-2.85, P = 0.009). The 5-year survival rate in the 2DRT and 3DCRT groups was 73.0% and 82.3%, P = 0.007, respectively. Cervical cancer patients treated with 3DCRT had better overall survival.
[Show abstract][Hide abstract] ABSTRACT: Many studies have reported excess cancer mortality in patients with mental illness. However, scant studies evaluated the differences in cancer treatment and its impact on survival rates among mentally ill patients. Oral cancer is one of the ten most common cancers in the world. We investigated differences in treatment type and survival rates between oral cancer patients with mental illness and without mental illness.
Using the National Health Insurance (NHI) database, we compared the type of treatment and survival rates in 16687 oral cancer patients from 2002 to 2006. The utilization rate of surgery for oral cancer was compared between patients with mental illness and without mental illness using logistic regression. The Cox proportional hazards model was used for survival analysis.
Oral cancer patients with mental disorder conferred a grave prognosis, compared with patients without mental illness (hazard ratios [HR] = 1.58; 95% confidence interval [CI] = 1.30-1.93; P<0.001). After adjusting for patients' characteristics and hospital characteristics, patients with mental illness were less likely to receive surgery with or without adjuvant therapy (odds ratio [OR] = 0.47; 95% CI = 0.34-0.65; P<0.001). In multivariate analysis, oral cancer patients with mental illness carried a 1.58-times risk of death (95% CI = 1.30-1.93; P<0.001).
Oral cancer patients with mental illness were less likely to undergo surgery with or without adjuvant therapy than those without mental illness. Patients with mental illness have a poor prognosis compared to those without mental illness. To reduce disparities in physical health, public health strategies and welfare policies must continue to focus on this vulnerable group.
[Show abstract][Hide abstract] ABSTRACT: Lymph node yield is recommended as a benchmark of quality care in colorectal cancer. The objective of this study was to evaluate the impact of various factors upon lymph node yield and to identify independent factors associated with lymph node harvest.
The records of 162 patients with Stage I to Stage III colorectal cancers seen in one institution were reviewed. These patients underwent radical surgery as definitive therapy; high-risk patients then received adjuvant treatment. Pathologic and demographic data were recorded and analyzed. The subgroup analysis of lymph node yields was determined using a t-test and analysis of variants. Linear regression model and multivariable analysis were used to perform potential confounding and predicting variables.
Five variables had significant association with lymph node yield after adjustment for other factors in a multiple linear regression model. These variables were: tumor size, surgical method, specimen length, and individual surgeon and pathologist. The model with these five significant variables interpreted 44.4% of the variation.
Patients, tumor characteristics and surgical variables all influence the number of lymph nodes retrieved. Physicians are the main gatekeepers. Adequate training and optimized guidelines could greatly improve the quality of lymph node yields.